2, 5-dialkoxy-3, 4-dihydroxytetrahydrofurans and their hydrolysates, and methods of producing them



2,5 DIALKOXY 3,4 DIHYDROXYTETRAHYDRO- FURANS AND THEIR HY DROLYSATES,AND METHODS OF PRODUCING THEM Niels Konrad Friedrich WilhelmClauson-Kaas, Klampenberg, Denmark, assignor to A/S Sadolin & Holmblad,Copenhagen, Denmark No Drawing. Application June 23, 1952, Serial No.295,126

Claims priority, application Denmark JulyS, 1951 9Claims. or. 260-3414)This invention relates to 2,5 ,-dialkoxy-3,4-dihydroxytetrahydrofuransof the general formula:

no i on EFL JiRl no O oa where R designates alkyl groups, and R1, R2, R3and R designate hydrogen, alkyl groups or aliphatic groups containingonly carbon, hydrogen and oxygen atoms.

The invention further relates to hydrolysates of the said components andto methods for the production of the compounds and hydrolysates.

The compounds of the invention are hitherto unknown substances which areacetals of 2,3-dihydroxy-L4-dicar bonyl compounds. By the hydrolysisdicarbonyl compounds are obtained, which are useful as intermediates inthe synthesis of alkaloids of the tropinone series and may also find usein the production of otherwise difiicultly accessible carbohydrates.

The objects of the invention will appear from the above and from thefollowing detailed description of preferred embodiments of theinvention, but it should be understood that the scope of the inventionis not to be limited by the following particulars, since modificationswill be obvious to anyone skilled in the art.

According to the invention 2,5-dialkoxy-2,5-dihydrofurans of thefollowing general formula:

R4 LR] R07 OR where R, R1, R2, R3 and R4 have the above significance,are treated with an oxidizing agent, which hydroxylates the double bond,whereafter the resulting 3,4-dihydroxy compounds are isolated and, ifdesired, hydrolyzed in known manner. An alkali permanganate, such aspotassium permanganate, is preferably used as the oxidizing agent, andthe oxidation is expediently carried out in aqueous solution at atemperature below C.

The 2,5-dialkoxy-2,S-dihydrofurans used in the reaction are preferablythose which are produced as described in my co-pending application,Serial No. 163,801, filed May 23, 1950 now abandoned.

Using 2,5-dimethoxy-2,5-dihydrofuran as a starting material, thereaction is illustrated by the following scheme:

HO OH H 0 01 0 CH: O 0

nitcd States PatentO '2 furan may be hydrolyzed to tartaric dialdehydeaccording to the following scheme:

HO OH 1' E B100 0 OCH! In the following the invention will beillustrated by some examples.

HO OH 2011.0 CH0 CH0 Example 1 Thepermanganateis-usedmomentaneously. Bya short hatingto-65 C. the col-loidally precipitated manganese dioxide.is brought into a filterable form and may be filtered on: after cooling.The manganese dioxide is further washed with 300 ccs. of water, whichare added to the filtrate. 750 g. of potassium carbonate are also added,and the filtrate isthen continuously extractedwith ether. The ethersolution is dried with sodium sulphate and evaporated in vacuum. Theresidue, amounting to 26 g., is distilled in vacuum. Thereby 10.2 g. or26% of 3 the starting material is regained and there is further obtained13.5 g. of 2,5-dimethoxy-3,4-dihydroxy-tetrahydrofuran, the boilingpoint of which at 11 mm. of mercur y is C., and the refractive index nat 25 C. of which is 1.452-1.454. The product is a colourless, viscousoil, in some casescrystallizing partly. It is probably a mixture ofdilferent stereoisomers.

Probably, the product is a mixture of different stereoisomers.

The oxidation may also be carried out at a lower temperature, for instance' at 20 C., using a mixture of acetone and water as a solvent, theyield being about the same as by the above method.

The tetrahydrofurans may be hydrolyzed as follows.

0.25 g. of 2,5-dimethoxy-3,4-dihydroxy-tetrahydrofuran are dissolved in2 ccs. of decinormal sulphuric acid and left standing for 3 hours atroom temperature. Thereby tartaric dialdehyde is formed and may beisolated as a bis-phenylhydrazone in the following manner. 2 ccs. ofwater, 3-normal acetic acid solution and 4-normal sodium acetatesolution, respectively, are added together with 0.4 ccs. ofphenylhydrazine. A slightly yellow precipitate of bis-phenylhydrazone isrecovered and re-crystallized from acetone-benzene and is now pure whitewith melting point 193l94 C.

Example 2 The method described in Example 1 is applied to 15.8 g. (0.10mole) of 2,5-diethoxy-2,S-dihydrofuran resulting in 5.5 g. of2,5-diethoxy-3,4-dihydroxy-tetrahydrofuran, which is a colourless oil,the boiling point of which at 9 mm. is 157-158 C. and the refractiveindex of which 21 at 25 C. is 1.449.

Example 3 Applying the method of Example 1 to 18.6 g. (0.10 mole) ofdi-n-propoxy-2,S-dihydrofuran results in 4.1 g. of2,5-di-n-propoxy-3,4-dihydroxy-tetrahydrofuran which is a colourlessliquid boiling at 171-172 C. at 9 mm. and having the refractive index nat 25 C.=l.447.

Example 4 Using 18.6 g. (0.10 mole) of 2,5-diisopropoxy-2,5-dihydrofuranas a starting material in a method as described in Example 1, 6.9 g. of2,5-diisopropoxy-3,4-dihydroxytetrahydrofuran are obtained as colourlesscrystals, melting at 51-52 C.

Example 20.2 g. of 2,5-dimethoxy-2,S-dihydrofurfuryl acetate (0.10 mole)are dissolved in 200 cos. of water and 12.0 g. of potassium permanganate(0.076 mole) dissolved in 300 cos. of water are added during 30 minutesas described in Example 1. Then 71.5 cos. of normal sulphuric acid and1.0 cos. of normal acetic acid are added, and the mixture is extractedcontinuously with benzene during hours. From the solution in benzene7.96 g.=39% of the starting material may be regained. From the aqueousphase manganese dioxide is removed by filtration, and the filtrate isextracted continuously with ether during 24 hours. The ethereal solutionyields 2.27 g. of 2,5-dimethoxy-3,4-dihydroxy-tetrahydrofurfurylacetate, B. P.o.4=133-137 C., n =1.460.

Example 6 Example 7 20.4 g, of 2,5dimethoxy-2,S-dihydrofurfuryldimethylacetal (0.10 mole) is reacted as described in Example 1, whereby3.8 g. of the starting material is regained, and there is obtained 0.7g. of 2,5 dimethoxy 3,4- dihydroxy-tetrahydrofurfuraldimethyl acetal,

B. P.1e=171-175 C., n =l.453

I claim:

1. 2,5 dialkoxy 3,4 dihydroxy tetrahydrofurans of the general formula:

atoms and R1 is selected from the group consisting of hydrogen, an alkylgroup containing less than 4 carbon atoms, and the following saturatedaliphatic groups comprising carbon, hydrogen and oxygen only, containingless than 4 carbon atoms: CH2O-(lower fatty acid acyl); CH(O-loweralkyl)2; and COO-(lower alkyl).

2. 2,5-dimethoxy-3,4-dihydroxy-tetrahydrofuran.

3. 2,5-diethoXy-3,4-dihydroxy-tetrahydrofuran.

4. 2,5-dimethoxy-3,4 dihydroxy tetrahydrofurfuryl acetate.

5. 2,5-dirnethoxy 3,4 dihydroxy tetrahydropyromusic acid methyl ester.

6. 2,5 dimethoxy-3,4 dihydroxy-tetrahydrofurfural dimethyl acetal.

7. 2,5-di(lower alkoxy)-3,4-dihydroxytetrahydrofuran.

8. A method for the production of a 2,5-dia1koxy-3,4-dihydroxytetrahydrofuran which comprises treating a 2,5-dialkoxy-2,5-dihydrofuran of the general formula R] R1 0 0a withpotassium permanganate in an aqueous solution at a temperature below 5C., where R is an alkyl group containing less than 7 carbon atoms and R1is selected from the group consisting of hydrogen, an alkyl groupcontaining less than 4 carbon atoms, and the following saturatedaliphatic groups comprising carbon, hydrogen and oxygen only, containingless than 4 carbon atoms: -CH2O (lower fatty acid acyl); --CH(O-loweralkyl).-;; and -COO-(lower alkyl).

9. The method of claim 8, wherein the tetrahydrofuran is furtherhydrolyzed to a dicarbonyl compound.

. 7 References Cited in the file of this patent Sheehan et al.: JACS 74,pp. 3825-28 (recd Jan. 7,

1952). Bergmann et al.': Berichte 63, pp. 1911-17 (1930).

1. 2,5 - DIALKOXY -3,4- DIHYDROXY - TETRAHYDROFURANS OF THE GENERALFORMULA: